It has been well established that tumor growth and metastasis critically depends on the process of angiogenesis and that integrins and growth factor receptors function in a cooperative manner to regulate cellular behavior. Integrin alpha V beta 5 is known to cooperate with growth factor receptors and promote intracellular signaling events that influence cell migration, proliferation and survival. Interestingly, alpha V beta 5 promotes cell attachment to vitronectin, however, growth factor stimulation is required in order to potentiate cell migration on this substrate, or lead to tumor cell metastasis in vivo. Specifically, alpha V beta 5 dependent downstream signaling, and cell migration were found to depend upon cytokine-activated Src kinase. Growth factors/cytokines activate Src kinase, which induces the phosphorylation of tyrosine residue 861 within the focal adhesion kinase (FAK) COOH-terminus, facilitating the assembly of a FAK/alpha V beta 5 complex both in vivo and in vitro. However, the specific interactions between FAK and alpha V beta 5 are poorly understood. Therefore, it is our hypothesis that growth factor activation of Src mediates the assembly of a FAK/?alpha V beta 5 signaling complex which influences cell migration or invasion in vitro and tumor cell metastasis in vivo. We will investigate the specific interactions between FAK and beta 5 integrins mediated by Src activation in cell migration and tumor cell metastasis.